Translational quantitative systems toxicology to improve the understanding of the safety of medicines

The development of all new medicines requires extensive nonclinical and clinical testing prior to drug approval by regulatory agencies and consequent marketing launch. Although clinical trials are generally conducted safety based on nonclinical results, a significant number of potential medicines (drug candidates) fail during clinical testing due to safety signals in human subjects, and high profile safety failures do occur. Thus, determining when nonclinical results reflect increase clinical risk prior to clinical testing remains challenging.

The TransQST project is gathering together existing data and will generate new data under the project goals to support the development of tools that should make it easier to assess the safety profile of drug candidates before undergoing clinical testing phase. This will be achieved by an increased understanding of when results in nonclinical testing can be reliably extrapolated to humans, and by developing models to predict exposure-based biological responses in human tissues, which is an important element of safety assessment for all new drug candidates. Since liver, kidney, cardiovascular and gastrointestinal-immune systems are among more common target organs when safety signals are encountered during clinical testing, TransQST work focuses on these four systems.

During the project’s life participants envisage also working toward improved methods to visualise and analyse large and complex datasets covering different types of available information (ie. drug metabolism, transcriptomics, proteomics, metabolomics, toxicology, pathological phenotype, biomarkers) to aid decision making on drug safety.

Aknowledgement

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116030. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.